Silver Benzoate Facilitates the Copper-Catalyzed C-N Coupling of Iodoazoles with Aromatic Nitrogen Heterocycles

Cedric Lozano; Cristian Ramirez; Ny Sin; Hélène M-F Viart; Stanley B Prusiner; Nick A Paras; Jay Conrad

doi:10.1021/acsomega.1c00458

Silver Benzoate Facilitates the Copper-Catalyzed C-N Coupling of Iodoazoles with Aromatic Nitrogen Heterocycles

ACS Omega. 2021 Mar 31;6(14):9804-9812. doi: 10.1021/acsomega.1c00458. eCollection 2021 Apr 13.

Authors

Cedric Lozano¹, Cristian Ramirez¹, Ny Sin^{1

2}, Hélène M-F Viart^{1

2}, Stanley B Prusiner^{1

2

3}, Nick A Paras^{1

2}, Jay Conrad^{1

2}

Affiliations

¹ Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California 94158, United States.
² Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco 94158, California, United States.
³ Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California 94158, United States.

Abstract

In the literature, C-N coupling methods for the reaction of iodo-oxazole with 2-pyridinone were found to be low yielding. C-N coupling using silver benzoate additives with CuI catalysts and 4,7-dimethoxy-1,10-phenanthroline ligands has been developed to afford synthetically useful yields of the desired heterobicycle product. The reaction conditions are applied to the coupling of a range of iodo-heterocycles with 2-pyridinone. The coupling of a variety of NH-containing heterocycles with 4-iodo-oxazole is also demonstrated. The use of 2-, 4-, or 5-iodo-oxazole allows for the coupling of pyridinone to each oxazole position.